砷与蛋白相互作用研究进展

Interaction of Arsenic Species with Proteins

本文综述了砷与不同蛋白相互作用的研究,比较了不同形态砷与蛋白结合能力的差异,进而讨论了砷的毒性与形态的关系。砷摄入体内后首先会进入血液,部分与血液中的蛋白结合,结合态和游离态的砷化合物随着血液循环到达各个器官、组织,甚至进入细胞内部与其他功能蛋白、受体、酶等发生直接或间接的相互作用,从而影响各种蛋白等活性分子的正常生理活动。在这过程中,不同形态砷的毒性也会体现在与蛋白相互作用能力的强弱上。同时,砷的解毒过程也在进行着,人们在ars操纵子中发现的两种去毒性蛋白与砷的相互作用被认为是将砷从细胞内排出,从而去除砷毒性的有效机制。

One of the mechanisms of arsenic toxicity is believed to be caused by arsenic interaction with proteins, resulting in the inhibition of the bioactivities of proteins. This article briefly summarizes recent studies on interaction between arsenic species and proteins, compares the binding ability of different arsenic species to proteins, and discusses the relationship between speciation and toxicity of arsenic. Complementary chromatography, inductively coupled plasma mass spectrometry, and electrospray tandem mass spectrometry techniques enabled the detection of protein-bound arsenic species, characterization of binding stoichiometry, and identification of binding sites in proteins. An application of these techniques to studies of arsenic binding to rat hemoglobin has resulted in the finding of a reactive cysteine （cysteine 13 in the alpha chain） that is responsible for the retention of arsenic in rat blood. Studies of arsenic binding to other proteins, for example enzymes, receptors, and ars operons, have also led to improved understanding of the toxicity and transport of arsenic species.